The perturbation of metabolic and physiologic processes in host tissues observed in insulin-dependent diabetes mellitus (IDDM) may be relevant to the pathogenesis of periodontal disease. However, previous studies attempting to relate these two disease entities have yielded conflicting data. Most of the studies were retrospective or of cross-sectional, epidemiologic design and had inadequate assessment of both the diabetes and periodontal disease parameters. Polymorphonuclear leukocyte (PMNL) dysfunction has been reported in both periodontal disease and diabetes. Thus, we hypothesize that following the onset of IDDM, PMNLs will become increasingly dysfunctional, clinical parameters of periodontal disease will show increasing values, degradation of the gingival connective tissue will occur, and collagen breakdown products will be washed out into the gingival crevice to appear in the gingival crevicular fluid and ultimately in the oral, cavity. Blood and mouth rinse samples will be collected at 3-6 months intervals from these prediabetic relatives of probands with IDDM. These fluids will be analyzed to provide data that will test the proposed hypotheses with experiments designed to achieve the following specific aims: 1) Determine islet cell antibodies and insulin autoantibodies. 2) Determine glycated hemoglobin. 3) Determine first-phase insulin response and serum glucose in intravenous glucose tolerance test. 4) Determine serum glucose in the oral glucose tolerance test. 5) Assess phagocytosis, of peripheral PMNLs. 6) Determine total hydroxyproline in hydrolyzed mouth rinse samples to assess collagen breakdown products released from the gingival crevices. 7) Assess the following clinical parameters of periodontal disease: Plaque Index, Gingival Index, Bleeding on Probing, Pocket Depth and Attachment Level. The proposed study will be prospective, have patients with well-characterized diabetic status, and use sensitive biochemical methods of assessing periodontal disease activity that will be analyzed for possible correlation with traditional clinical measures. The data from these proposed studies should provide new insights into the relationship between these two diseases and shed light on the mechanisms of both periodontal disease and some sequelae of IDDM.